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| ID | Type | Description | Link |
|---|---|---|---|
| 12-EI-0167 |
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Background:
Objectives:
Eligibility:
You may be able to take part in this study if you:
Design:
Objective: The objective of this study is to evaluate the safety of ocular NT-501 device with encapsulated NT-201 cells releasing Ciliary Neurotrophic Factor (CNTF) to the retina of participants affected with CNGB3 achromatopsia.
Study Population: Five participants affected with CNGB3 achromatopsia will be enrolled, with one eye treated per participant.
Design: This is a Phase I/II, prospective, single-center study. One eye of each participant will receive a vitreous NT-501 device implant releasing CNTF. The study will be completed once the final participant has received three years of follow-up.
Outcome Measures: The primary outcome is the number and severity of adverse events and systemic and ocular toxicities at six months post-implantation. Additional safety of ocular CNTF implants in participants with CNGB3 achromatopsia will be determined from assessment of retinal function, ocular structure and occurrence of adverse events at all time points. Secondary outcomes include changes in visual function including visual acuity and color vision, electroretinogram (ERG) responses, and retinal imaging with optical coherence tomography (OCT).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NT-501 CNTF-releasing implant | Experimental | Ocular implantation of a NT-501 CNTF-releasing capsule (20 ng/day) in one eye (the study eye) at baseline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NT-501 CNTF-releasing implant | Biological | 20 ng/day released into the eye |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Adverse Events at Six Months Post-Implantation | The primary outcome is the total number of adverse events reported within six months post-implantation. | Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation |
| Number of Severe Adverse Events at Six Months Post-Implantation | The number of severe adverse events reported within six months post-implantation. | Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation |
| Number of Ocular Adverse Events at Six Months Post-Implantation | The number of eye-related adverse events reported within six months post-implantation. | Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation |
| Number of Non-Ocular Adverse Events at Six Months Post-Implantation | The number of non eye-related adverse events reported within six months post-implantation. | Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Adverse Events at All Time Points Post-Implantation | The total number of adverse events reported from Day 1 post-implantation through study completion at Year 3. | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
| Number of Severe Adverse Events at All Time Points Post-Implantation |
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Inclusion Criteria:
To be eligible, the following inclusion criteria must be met, where applicable.
Exclusion Criteria:
A participant is not eligible if any of the following exclusion criteria are present.
Study Eye Eligibility Criteria:
The participant must have at least one eye meeting all inclusion criteria and none of the exclusion criteria listed below.
Study Eye Inclusion Criteria:
The study eye must have a best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity letterscore of ≤ 53 (i.e., ≤ 20/100). The visual acuity from the first baseline visit (Baseline 1) will be used for eligibility determination in case of a change in visual acuity at the second baseline visit (Baseline 2).
Study Eye Exclusion Criteria:
Study Eye Selection Criteria in Cases of Bilateral Disease:
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| Name | Affiliation | Role |
|---|---|---|
| Paul A Sieving, MD, PhD | National Eye Institute (NEI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10958649 | Background | Kohl S, Baumann B, Broghammer M, Jagle H, Sieving P, Kellner U, Spegal R, Anastasi M, Zrenner E, Sharpe LT, Wissinger B. Mutations in the CNGB3 gene encoding the beta-subunit of the cone photoreceptor cGMP-gated channel are responsible for achromatopsia (ACHM3) linked to chromosome 8q21. Hum Mol Genet. 2000 Sep 1;9(14):2107-16. doi: 10.1093/hmg/9.14.2107. | |
| 11536077 |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | NT-501 CNTF-releasing Implant | Participants received an ocular implantation of a NT-501 CNTF-releasing capsule (20 ng/day) in one eye (the study eye) at baseline. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | NT-501 CNTF-releasing Implant | Participants received an ocular implantation of a NT-501 CNTF-releasing capsule (20 ng/day) in one eye (the study eye) at baseline. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Adverse Events at Six Months Post-Implantation | The primary outcome is the total number of adverse events reported within six months post-implantation. | Posted | Number | Adverse Events | Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation |
|
|
Adverse events were collected at all time points until study completion (up to Week 156 post-implantation).
The primary outcome is the number and severity of adverse events and systemic and ocular toxicities within six months post-implantation.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NT-501 CNTF-releasing Implant Events ≤ 6 Months Post-implant | Participants received an ocular implantation of a NT-501 CNTF-releasing capsule (20 ng/day) in one eye (the study eye) at baseline. The events listed reflect the primary outcome endpoint of adverse events reported within 6 months post-implantation. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Uveitis | Eye disorders | MedDRA (16.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthropod Bite | Injury, poisoning and procedural complications | MedDRA (16.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Paul A Sieving, MD, PhD | National Eye Institute | 301-496-2234 | ps261o@nih.gov |
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| ID | Term |
|---|---|
| D005128 | Eye Diseases |
| D003117 | Color Vision Defects |
| ID | Term |
|---|---|
| D014786 | Vision Disorders |
| D012678 | Sensation Disorders |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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The total number of severe adverse events reported from Day 1 post-implantation through study completion at Year 3. Although there were two serious adverse events (SAEs) reported during the study, only one event's severity was classified as "severe." |
| Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
| Number of Ocular Adverse Events at All Time Points Post-Implantation | The total number of eye-related adverse events reported from Day 1 post-implantation through study completion at Year 3. | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
| Number of Non-Ocular Adverse Events at All Time Points Post-Implantation | The total number of non eye-related adverse events reported from Day 1 post-implantation through study completion at Year 3. | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
| Number of Participants Who Experienced an Improvement in Visual Acuity of Greater Than 0.3 logMAR (Logarithm of the Minimum Angle of Resolution) Post-Implantation in the Study Eye. | Improvement of visual acuity was assessed on both the study and control eyes. Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. . The LogMAR scale [expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30)] converts the geometric sequence of a traditional chart to a linear scale. It measures VA loss; positive values indicate vision loss, whereas negative values denote normal or better VA. A lower LogMAR value indicates better VA. For example, a visual acuity of 20/20 corresponds to a logMAR value of zero (0), and a visual acuity of 20/100 corresponds to a LogMAR value of 0.7. | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
| Number of Participants Who Experienced an Improvement in Visual Acuity of Greater Than 0.3 logMAR (Logarithm of the Minimum Angle of Resolution) Post-Implantation in the Untreated Control Eye. | Improvement of visual acuity was assessed on both the study and control eyes. Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. . The LogMAR scale [expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30)] converts the geometric sequence of a traditional chart to a linear scale. It measures VA loss; positive values indicate vision loss, whereas negative values denote normal or better VA. A lower LogMAR value indicates better VA. For example, a visual acuity of 20/20 corresponds to a logMAR value of zero (0), and a visual acuity of 20/100 corresponds to a LogMAR value of 0.7. | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
| Number of Participants Who Experienced an Increase in Either the Rod or Cone Electroretinogram (ERG) Responses of More Than 75% Post-Implantation in the Study Eye. | Full-field ERGs were recorded according to International Society of Clinical Electrophysiology of Vision Standards (ISCEV). | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
| Number of Participants Who Experienced an Increase in Either the Rod or Cone Electroretinogram (ERG) Responses of More Than 75% Post-Implantation in the Untreated Control Eye. | Full-field ERGs were recorded according to International Society of Clinical Electrophysiology of Vision Standards (ISCEV). | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
| Number of Participants Who Experienced an Improvement in Color Discrimination and/or Matching Post-Implantation in the Study Eye. | Color hue discrimination was tested by the Nagel anomaloscope, American Optical Hardy Rand Rittler (AOHRR) color plates, and a low vision version of the Cambridge Color Test (LvCCT) implemented on a ViSaGe System (Cambridge Research Systems Ltd., Rochester, UK) using custom-written software. Hardy Rand Rittler testing followed the guidelines accompanying the test and administered under a Macbeth Lamp at 300 lux. | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
| Number of Participants Who Experienced an Improvement in Color Discrimination and/or Matching Post-Implantation in the Untreated Control Eye. | Color hue discrimination was tested by the Nagel anomaloscope, American Optical Hardy Rand Rittler (AOHRR) color plates, and a low vision version of the Cambridge Color Test (LvCCT) implemented on a ViSaGe System (Cambridge Research Systems Ltd., Rochester, UK) using custom-written software. Hardy Rand Rittler testing followed the guidelines accompanying the test and administered under a Macbeth Lamp at 300 lux. | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
| Wissinger B, Gamer D, Jagle H, Giorda R, Marx T, Mayer S, Tippmann S, Broghammer M, Jurklies B, Rosenberg T, Jacobson SG, Sener EC, Tatlipinar S, Hoyng CB, Castellan C, Bitoun P, Andreasson S, Rudolph G, Kellner U, Lorenz B, Wolff G, Verellen-Dumoulin C, Schwartz M, Cremers FP, Apfelstedt-Sylla E, Zrenner E, Salati R, Sharpe LT, Kohl S. CNGA3 mutations in hereditary cone photoreceptor disorders. Am J Hum Genet. 2001 Oct;69(4):722-37. doi: 10.1086/323613. Epub 2001 Aug 30. |
| 12077706 | Background | Kohl S, Baumann B, Rosenberg T, Kellner U, Lorenz B, Vadala M, Jacobson SG, Wissinger B. Mutations in the cone photoreceptor G-protein alpha-subunit gene GNAT2 in patients with achromatopsia. Am J Hum Genet. 2002 Aug;71(2):422-5. doi: 10.1086/341835. Epub 2002 Jun 20. |
| 25205868 | Result | Zein WM, Jeffrey BG, Wiley HE, Turriff AE, Tumminia SJ, Tao W, Bush RA, Marangoni D, Wen R, Wei LL, Sieving PA. CNGB3-achromatopsia clinical trial with CNTF: diminished rod pathway responses with no evidence of improvement in cone function. Invest Ophthalmol Vis Sci. 2014 Sep 9;55(10):6301-8. doi: 10.1167/iovs.14-14860. |
| years |
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| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| Primary | Number of Severe Adverse Events at Six Months Post-Implantation | The number of severe adverse events reported within six months post-implantation. | Posted | Number | Adverse Events | Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation |
|
|
|
| Primary | Number of Ocular Adverse Events at Six Months Post-Implantation | The number of eye-related adverse events reported within six months post-implantation. | Posted | Number | Adverse Events | Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation |
|
|
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| Primary | Number of Non-Ocular Adverse Events at Six Months Post-Implantation | The number of non eye-related adverse events reported within six months post-implantation. | Posted | Number | Adverse Events | Day 1, Week 1, Week 4, Week 12, Week 24 post-implantation |
|
|
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| Secondary | Number of Adverse Events at All Time Points Post-Implantation | The total number of adverse events reported from Day 1 post-implantation through study completion at Year 3. | Posted | Number | Adverse Events | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
|
|
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| Secondary | Number of Severe Adverse Events at All Time Points Post-Implantation | The total number of severe adverse events reported from Day 1 post-implantation through study completion at Year 3. Although there were two serious adverse events (SAEs) reported during the study, only one event's severity was classified as "severe." | Posted | Number | Adverse Events | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
|
|
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| Secondary | Number of Ocular Adverse Events at All Time Points Post-Implantation | The total number of eye-related adverse events reported from Day 1 post-implantation through study completion at Year 3. | Posted | Number | Adverse Events | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
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| Secondary | Number of Non-Ocular Adverse Events at All Time Points Post-Implantation | The total number of non eye-related adverse events reported from Day 1 post-implantation through study completion at Year 3. | Posted | Number | Adverse Events | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
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| Secondary | Number of Participants Who Experienced an Improvement in Visual Acuity of Greater Than 0.3 logMAR (Logarithm of the Minimum Angle of Resolution) Post-Implantation in the Study Eye. | Improvement of visual acuity was assessed on both the study and control eyes. Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. . The LogMAR scale [expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30)] converts the geometric sequence of a traditional chart to a linear scale. It measures VA loss; positive values indicate vision loss, whereas negative values denote normal or better VA. A lower LogMAR value indicates better VA. For example, a visual acuity of 20/20 corresponds to a logMAR value of zero (0), and a visual acuity of 20/100 corresponds to a LogMAR value of 0.7. | Posted | Number | participants | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
|
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| Secondary | Number of Participants Who Experienced an Improvement in Visual Acuity of Greater Than 0.3 logMAR (Logarithm of the Minimum Angle of Resolution) Post-Implantation in the Untreated Control Eye. | Improvement of visual acuity was assessed on both the study and control eyes. Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. . The LogMAR scale [expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30)] converts the geometric sequence of a traditional chart to a linear scale. It measures VA loss; positive values indicate vision loss, whereas negative values denote normal or better VA. A lower LogMAR value indicates better VA. For example, a visual acuity of 20/20 corresponds to a logMAR value of zero (0), and a visual acuity of 20/100 corresponds to a LogMAR value of 0.7. | Posted | Number | participants | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
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| Secondary | Number of Participants Who Experienced an Increase in Either the Rod or Cone Electroretinogram (ERG) Responses of More Than 75% Post-Implantation in the Study Eye. | Full-field ERGs were recorded according to International Society of Clinical Electrophysiology of Vision Standards (ISCEV). | Posted | Number | participants | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
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| Secondary | Number of Participants Who Experienced an Increase in Either the Rod or Cone Electroretinogram (ERG) Responses of More Than 75% Post-Implantation in the Untreated Control Eye. | Full-field ERGs were recorded according to International Society of Clinical Electrophysiology of Vision Standards (ISCEV). | Posted | Number | participants | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
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| Secondary | Number of Participants Who Experienced an Improvement in Color Discrimination and/or Matching Post-Implantation in the Study Eye. | Color hue discrimination was tested by the Nagel anomaloscope, American Optical Hardy Rand Rittler (AOHRR) color plates, and a low vision version of the Cambridge Color Test (LvCCT) implemented on a ViSaGe System (Cambridge Research Systems Ltd., Rochester, UK) using custom-written software. Hardy Rand Rittler testing followed the guidelines accompanying the test and administered under a Macbeth Lamp at 300 lux. | Posted | Number | participants | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
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| Secondary | Number of Participants Who Experienced an Improvement in Color Discrimination and/or Matching Post-Implantation in the Untreated Control Eye. | Color hue discrimination was tested by the Nagel anomaloscope, American Optical Hardy Rand Rittler (AOHRR) color plates, and a low vision version of the Cambridge Color Test (LvCCT) implemented on a ViSaGe System (Cambridge Research Systems Ltd., Rochester, UK) using custom-written software. Hardy Rand Rittler testing followed the guidelines accompanying the test and administered under a Macbeth Lamp at 300 lux. | Posted | Number | participants | Day 1, Week 1, Week 4, Week 12, Week 24, Week 52, Week 78, Week 156 post-implantation |
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| 1 |
| 5 |
| 5 |
| 5 |
| EG001 | NT-501 CNTF-releasing Implant Events > 6 Months Post-implant | Participants received an ocular implantation of a NT-501 CNTF-releasing capsule (20 ng/day) in one eye (the study eye) at baseline. The events listed are adverse events reported after the primary outcome endpoint of 6 months post-implantation. | 1 | 5 | 2 | 5 |
| Retinal Detachment | Eye disorders | MedDRA (18.1) | Systematic Assessment |
|
| Delayed Dark Adaptation | Eye disorders | MedDRA (16.0) | Systematic Assessment | The event coded to a MedDRA v16 Preferred Term of Night Blindness but the verbatim Lower Level Terminology is delayed dark adaptation. As the MedDRA term may misrepresent participants as being blind, the verbatim event will be utilized, not MedDRA. |
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| Uveitis | Eye disorders | MedDRA (16.0) | Systematic Assessment |
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| Vitreous detachment | Eye disorders | MedDRA (16.0) | Systematic Assessment |
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| Vitritis | Eye disorders | MedDRA (15.1) | Systematic Assessment |
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| Shoulder Operation | Surgical and medical procedures | MedDRA (18.1) | Systematic Assessment |
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| Lenticular Opacities | Eye disorders | MedDRA (18.1) | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA (18.1) | Systematic Assessment |
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| Uterine operation | Surgical and medical procedures | MedDRA (18.1) | Systematic Assessment |
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| D000077765 |
| Cone Dystrophy |
| D015785 | Eye Diseases, Hereditary |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |